EP2 Receptor Signaling Pathways Regulate Classical Activation of Microglia

• DOI: 10.1074/jbc.m113.455816
• Publication Date: 2013-02-13T04:56:45Z
• Authors: Yi Quan; Jianxiong Jiang; Ray Dingledine
• Keywords: Prostaglandin E2 receptor

Activation of EP2 receptors by prostaglandin E2 (PGE2) promotes brain inflammation in neurodegenerative diseases, but the pathways responsible are unclear. couple to Gαs and increase cAMP, which associates with protein kinase A (PKA) cAMP-regulated guanine nucleotide exchange factors (Epacs). Here, we studied function its signaling rat microglia their resting state or undergoing classical activation vitro following treatment low concentrations lipopolysaccharide interferon-γ. Real time PCR showed that PGE2 had no effect on expression CXCL10, TGF-β1, IL-11 exacerbated rapid up-regulation mRNAs encoding cyclooxygenase-2, inducible NOS, IL-6, IL-1β blunted production TNF-α, IL-10, CCL3, CCL4. These effects were mimicked fully agonist butaprost only weakly EP1/EP3 17-phenyl trinor EP4 CAY10598 not at all EP3/EP1 sulprostone confirmed measurements TNF-α. In microglia, induced cAMP formation altered mRNA inflammatory mediators, was unchanged. The PKA inhibitor H89 little mediators modulated EP2, whereas Epac activator 8-(4-chlorophenylthio)-2'-O-methyladenosine 3',5'-cyclic monophosphate acetoxymethyl ester effects. results indicate plays a complex immune regulatory role during prominent this role.